Survey of body donation programs in the US concerning the use of donor personal information with medical students.
Body donor programs need to balance ethical concerns and educational needs. Among donor programs in the US, there is variability in the amount of donor personal information that is provided to medical students. This study assesses this variability and investigates the reasons for the variability among donor programs. Telephone interviews and email surveys were used to collect information concerning the provision and use of donor personal information with medical students. One hundred fifty-one donor programs in the US were contacted via email or telephone interview or both. Fifty-three donor programs responded to the survey or participated in the telephone interview. The survey results show variation, not only in the amount of donor personal information provided to medical students, but also in the attitudes and beliefs of the donor program personnel concerning donor personal information. This research documents the variability of the educational use of donor personal information. It is hoped that this description of the various approaches to using donor information will encourage the ethical use of donor information within the context of medical education. Clin. Anat. 30:445-449, 2017. © 2017 Wiley Periodicals, Inc.


[Surgical treatment of combined injuries of the neck and shoulder joints].
To develop the algorithm for effective surgical restoration of shoulder joint and neck functions and acceleration of social and labor rehabilitation. There were 116 patients with combined consequences of burns of the neck and shoulder joints between 2012 and 2021. These ones amounted to 29.4% of all patients with lesions of the neck or shoulder joints. Simultaneous surgeries with correction of post-burn cicatricial deformities and contractures were performed in 66 patients (56.9%). Age of patients ranged from 18 to 72 years, and 96% of them were employable. There were 89 (76.7%) women and 27 (23.3%) men. We assessed spread and localization of cicatricial process, as well as restriction of mobility of the neck and shoulder joint to select optimal surgical approach. Classification of neck deformities and contractures of shoulder joints considering severity of cicatricial lesion and functional impairment made it possible to systematize the approach to reconstructive procedures. Reconstructive surgery included repair with local tissues including skin-fatty flap, non-perforated split or full-thickness skin autograft, rotated flaps including those based on perforator vessels, as well as preliminary skin stretching. In general, 116 patients with combined lesions of the neck and shoulder joints underwent 314 surgeries. To accelerate rehabilitation, we performed simultaneous surgeries with correction of deformities and contractures in 66 patients (56.9%). Staged reconstructive surgeries were carried out in 50 patients. Acute dermotension and skin-fatty neck flap grafting were the most common for deformities and contractures of the neck. Skin-fatty axillary flap was used in most patients with contractures of shoulder joints. Simultaneous surgeries can accelerate rehabilitation. Correct algorithm of staged surgical treatment reduces rehabilitation period and eliminates functional disorders.


The association of body composition assessment with hospital length of stay in off-pump coronary artery bypass patients.
Bioelectrical impedance analysis is a widely available, non-invasive method for body composition assessment. To elucidate the perioperative body composition alterations and their prognostic utility for hospital length of stay (LOS) in low risk, off-pump coronary artery bypass (OPCAB) patients. Fifty patients undergoing elective OPCAB were included in the study. Body composition assessments were performed 1 day before the scheduled surgery and on the 6th postoperative day. Patients were grouped into < 9 days (n = 29, 58%) and ≥ 9 days (n = 21, 42%). Multivariate logistic regression analysis was performed to create a body composition-based screening panel for prolonged hospital stay. No significant differences in anthropometric measurements, clinical characteristics or occurrence of postoperative complications were detected between the study groups. Patients with longer hospitalization had significantly higher content of fat mass (FM%) and fat mass index (FMI), and significantly lower content of fat free mass (FFM%) baseline parameters (p = 0.011, p = 0.04 and p = 0.012, respectively). High FM% values had 15-fold, low FFM% values had 13-fold and high FMI values had 7-fold higher risk of experiencing longer stay in the hospital (p = 0.001, p = 0.001 and p = 0.005, respectively). The combined panel of three variables (higher FM%, lower FFM% and higher FMI) had 16-fold higher risk of longer hospitalization (adjusted OR = 16.40; 95% CI: 3.52-76.34; p = 0.0004). Preoperative high FM and low FFM content are independent predictors of prolonged hospital length of stay in normal- and increased-BMI patients after OPCAB.


Prognostic value of inflammatory biomarkers for predicting the extent of lung involvement and final clinical outcome in patients with COVID-19.
Inflammation plays a major role in coronavirus disease (COVID-19). Factors that convey information about the status of inflammation could predict disease severity and help identify patients prone to clinical deterioration. Here, we aimed to evaluate the predictive value of inflammatory markers on the extent of lung involvement and survival of patients with COVID-19. Eighty patients with confirmed COVID-19 were enrolled. Demographic, clinical, and laboratory data were collected at admission. All patients underwent chest computed tomography (CT); the extent of lung involvement was assessed by a scoring system. Patients were followed up until death or discharge occurred. Logistic regression analysis was performed to evaluate the association of investigated variables with COVID-19-related death. The association between different variables and CT score was assessed using linear regression model. Receiver operator characteristic curve analysis was applied to identify the predictive value of inflammatory markers and CT score on survival. The mean age of patients was 54.2 ± 15.2 years; 65% were male. Increased neutrophil-to-lymphocyte ratio (β =0.69, odds ratio [OR] =1.50), platelet-to-lymphocyte ratio (β =0.019, OR = 1.01), and decreased lymphocyte to C-reactive protein ratio (LCR) (β = -0.35, OR = 0.62) were significantly associated with a higher CT score and increased odds of death (P < 0.05). Lactate dehydrogenase level was also positively related with extensive lung involvement and death (β =1.15, OR = 1.52, P < 0.05). The LCR threshold for identifying survivors from nonsurvivors was 0.53 (area under curve [AUC] =0.82, 78% sensitivity and 74% specificity). Lung involvement ≥50% on chest CT was an excellent predictor of death (AUC = 0.83, 81% sensitivity and 79% specificity). Daily-performed laboratory tests that represent inflammation have great value for predicting the amount of disease burden and risk of mortality. Moreover, their cost-effectiveness and feasibility turn them into ideal prognostic markers.


A new computational method to predict transcriptional activity of a DNA sequence from diverse datasets of massively parallel reporter assays.
In recent years, the dramatic increase in the number of applications for massively parallel reporter assay (MPRA) technology has produced a large body of data for various purposes. However, a computational model that can be applied to decipher regulatory codes for diverse MPRAs does not exist yet. Here, we propose a new computational method to predict the transcriptional activity of MPRAs, as well as luciferase reporter assays, based on the TRANScription FACtor database. We employed regression trees and multivariate adaptive regression splines to obtain these predictions and considered a feature redundancy-dependent formula for conventional regression trees to enable adaptation to diverse data. The developed method was applicable to various MPRAs despite the use of different types of transfected cells, sequence lengths, construct numbers and sequence types. We demonstrate that this method can predict the transcriptional activity of promoters in HEK293 cells through predictive functions that were estimated by independent assays in eight tumor cell lines. The prediction was generally good (Pearson's r = 0.68) which suggested that common active transcription factor binding sites across different cell types make greater contributions to transcriptional activity and that known promoter activity could confer transcriptional activity of unknown promoters in some instances, regardless of cell type.


Docetaxel-loaded PEG-albumin nanoparticles with improved antitumor efficiency against non-small cell lung cancer.
The aim of the present study was mainly to assess the advantage of docetaxel-loaded PEG-albumin nanoparticles (PEG-DANPs) against non-small cell lung cancer (NSCLC) compared with the commercial product of docetaxel (Aisu®) and docetaxel-albumin nanoparticles (DANPs). We made systematic assessments on these three drugs against NSCLC both in vitro and in vivo. Based on our experiments, PEG-DANPs showed a dose- and time-dependent efficacy in the in vitro cytotoxicity studies; the tumors growth and the metastases in the livers of NSCLC-bearing nude mice in vivo were reduced dmarkedly by PEG-DANPs, and the PEG-DANP-treated mice had a minimum of weight loss; furthermore, the mice which were treated with PEG-DANPs can survive longer than the other groups. In conclusion, the PEG-DANPs have the lowest side-effects, and the highest antitumor and metastases activity of the three drugs, and it may provide an alternative to patients with NSCLC.


Monoclonal antibody to Theiler's murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis.
Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease in mice. The mechanisms underlying the demyelination have not been fully elucidated. We have raised a mAb to TMEV (DA strain), H8, that reacts both with TMEV VP-1 and galactocerebroside (GC). In mouse brain cultures, cells positive for the mAb H8 epitope were double labeled with antibody to myelin basic protein, indicating that those cells were oligodendrocytes. Further, mAb H8 could immunostain myelin structures in frozen sections from mouse brains. When injected intravenously into mice with acute allergic encephalomyelitis, mAb H8 increased by 10-fold the size of demyelinated areas within the spinal cords. This is the first report demonstrating that an antibody to virus can enhance demyelination of a central nervous system disease. Ig fractions from the sera of mice with chronic TMEV infection had antibody(s) to GC, as well as to TMEV, as determined by ELISA. Furthermore, a competition ELISA for TMEV or GC antigen revealed that sera from these infected mice contained antibody(s) with the same specificity as mAb H8. Our results indicate that antibodies generated by immune response to TMEV can react with myelin and oligodendrocytes, and contribute to demyelination through an immune process.


Spermine depresses NMDA, K/AMPA and GABAA-mediated synaptic transmission in the rat hippocampal slice preparation.
The effects of spermine, an endogenous polyamine, were examined in area CA1 of the rat hippocampal slice preparation. Spermine, at low millimolar concentrations, rapidly and potently depressed NMDA and K/AMPA-mediated population EPSPs, and GABA-mediated monosynaptic population IPSPs. These effects contrast with its well-known potentiation of NMDA currents at lower concentrations. Our results raise the possibility that the large intracellular stores of spermine that are released after various neural insults could act as an endogenous neuroprotective mechanism by limiting excessive calcium entry.


[Gastro Intestinal Stromal Tumor--clinical and pathological presentation].
Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor identified by a positive immunostaining (KIT tyrosine kinase). Surgical resection is the primary treatment, but non-resectable and recurrent disease may be treated by specific tyrosine kinase inhibitors. This study evaluates the clinical and pathological presentation of a Danish GIST population. Retrospective evaluation of patients diagnosed, treated and/or followed under the GIST diagnosis at the Department of Surgery, Odense University Hospital, during the period from January 1995 to September 2006. 41 patients with GIST were identified (25 males, 16 females, median age 62 years). The predominant symptoms leading to the diagnosis were upper gastrointestinal bleeding and abdominal pain. The majority of tumors were located in the stomach (63%) or in the small intestine (22%). 95% of the patients had a complete surgical resection, whereas resection was impossible in 2 patients. Approximately (2)/3 of the patients had a low or medium risk of developing metastases according to tumor size and number of mitoses. 1 in 4 patients was treated with a tyrosine kinase inhibitor during the course of the disease. GIST is a rare mesenchymal tumor but due to immunostaining methods the detection rate is increasing. The clinical and pathological presentation of this Danish GIST population is comparable to international data.


Physicochemical characterization of pH-responsive and fusogenic self-assembled non-phospholipid vesicles for a potential multiple targeting therapy.
In order to obtain nanocarriers suitable for the delivery of drugs in the treatment of cancer, pH-responsive nanovesicles capable of facilitating fusion (fusogenic nanovesicles) were synthesized and then their physicochemical characteristics were modified. These nanovesicles were made by combining polysorbates having different physicochemical features with the aim of realizing multiple-targeting nanoformulations suitable for in vitro treatment of cancer cells. Tween21 and Tween80 were self-assembled at different molar concentrations resulting in pH-responsive fusogenic nanovesicles with an average size of less than 150nm, and a narrow size distribution (polydispersity index) value of less than 0.2. Hydrophobic and hydrophilic fluorescent probes were loaded inside the nanovesicles in order to study their pH-responsiveness and fusogenic properties and it was noted that this process did not modify their physicochemical features. The pH-responsiveness and fusogenic assay demonstrated that the nanovesicles containing Tween21 at different molar ratios were pH-responsive and interacted with a synthetic model of a biological membrane supplemented with Ca2+ in the incubation medium. Fifty percent (molar ratio) of Tween21 was replaced with Tween80, since Tween80 can promote the adsorption of apolipoproteins (A-E) onto the surfaces of nanovesicles without altering their pH-responsiveness or fusogenic properties. In fact this equivalent molar concentration of Tween21 and Tween80 also maintained their degree of interaction with the apolipoproteins (A-E). Doxorubicin hydrochloride-loaded nanovesicles were synthesized and physicochemically characterized in order to obtain nanoformulations suitable for anticancer treatment. The therapeutic nanovesicles showed physicochemical properties similar to those of empty nanoformulations, and maintained pH-responsiveness, fusogenic properties and targeting versus the apolipoproteins (A-E). The doxorubicin hydrochloride was loaded into the nanovesicles using both passive and pH gradient remote loading procedures. The latter provided the nanovesicles with an entrapment efficiency percentage of over 30%, which was much higher than the 10% that was obtained using the passive loading procedure. The entrapment efficiency improved up to 60% for the nanovesicles made from the same molar concentration of Tween21 and Tween80. The anticancer activity of doxorubicin hydrochloride-loaded nanovesicles was further tested in vitro using human neuroblastoma (SH-SY5Y) cells which respond to treatment with this chemotherapeutic drug, but the nanovesicles carrying it must cross the BBB by means of specific receptors before the drug can provide a therapeutic effect in vivo. The anticancer activity of these doxorubicin hydrochloride-loaded nanovesicles was time- and dosage- dependent, and the surfactant components making up the nanoformulations was also a determining factor in the efficiency of their activity. These nanovesicles could provide innovative nanotherapeutics for potential in vitro multidrug targeting therapy.


Cortical border-zone infarcts: clinical features, causes and outcome.
To report the clinical features, causes and outcome of cerebral cortical border-zone infarcts BZI (C-BZI). The authors prospectively included patients with MRI-confirmed C-BZI among individuals consecutively admitted in Stroke Unit. Forty-five patients presented C-BZI out of 589 with MRI-confirmed cerebral infarcts (7.6%). Particular clinical characteristics existed in C-BZI in comparison with other cerebral infarctions as a whole, including: (1) frequent transient symptoms at onset (27% vs 9%; p<0.001) and low severity score (NIHSS=3.1±3.0 vs 5.2±6.1; p=0.02); (2) early seizures in first 2 weeks (7/45 (15.6%) vs 12/544 (2.2%); p<0.001), even when focusing only on other infarctions involving the cerebral cortex (15.6% vs 4.3%; p<0.01); (3) heterogeneous clinical presentation but specific transcortical aphasia allowing a clinical suspicion of BZI before MRI; and (4) frequently associated internal carotid disease (69%), with subsequent early surgery in 75% of the cases. Following adapted care in stroke unit, C-BZIs' prognosis appeared good (Rankin score ≤2 at D90) for 82% of the patients. Some clinical features are overrepresented in such infarctions, including initial transient symptoms preceding the onset of a completed deficit, transcortical aphasia and early seizures. Despite lower initial severity, C-BZIs justify early management in stroke unit, often followed by carotid surgery, leading to an overall good prognosis.


Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus.
Aedes (Stegomyia) albopictus, also known as the Asian tiger mosquito, is a mosquito which originated in Asia. In recent years, it has become increasingly rampant throughout the world. This mosquito can transmit several arboviruses, including dengue, Zika and chikungunya viruses, and is considered a public health threat. Despite the urgent need of genome engineering to analyze specific gene functions, progress in genetical manipulation of Ae. albopictus has been slow due to a lack of efficient methods and genetic markers. In the present study, we established targeted disruptions in two genes, kynurenine hydroxylase (kh) and dopachrome conversion enzyme (yellow), to analyze the feasibility of generating visible phenotypes with genome editing by the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) system in Ae. albopictus. Following Cas9 single guide RNA ribonucleoprotein injection into the posterior end of pre-blastoderm embryos, 30%-50% of fertile survivors produced alleles that failed to complement existing kh and yellow mutations. Complete eye and body pigmentation defects were readily observed in G1 pupae and adults, indicating successful generation of highly heritable mutations. We conclude that the CRISPR/Cas9-mediated gene editing system can be used in Ae. albopictus and that it can be adopted as an efficient tool for genome-scale analysis and biological study.


Proportion of medication error reporting and associated factors among nurses: a cross sectional study.
A medication error (ME) is any preventable event that may cause or lead to inappropriate medication use or patient harm. Voluntary reporting has a principal role in appreciating the extent and impact of medication errors. Thus, exploration of the proportion of medication error reporting and associated factors among nurses is important to inform service providers and program implementers so as to improve the quality of the healthcare services. Institution based quantitative cross-sectional study was conducted among 397 nurses from March 6 to May 10, 2015. Stratified sampling followed by simple random sampling technique was used to select the study participants. The data were collected using structured self-administered questionnaire which was adopted from studies conducted in Australia and Jordan. A pilot study was carried out to validate the questionnaire before data collection for this study. Bivariate and multivariate logistic regression models were fitted to identify factors associated with the proportion of medication error reporting among nurses. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance. The proportion of medication error reporting among nurses was found to be 57.4%. Regression analysis showed that sex, marital status, having made a medication error and medication error experience were significantly associated with medication error reporting. The proportion of medication error reporting among nurses in this study was found to be higher than other studies.


[Genotype-dependent mice behavior in cognitive tasks. Effect of noopept].
The interstrain differences in performance of C57BL/6J, BALB/c and DBA/2J male mice in two cognitive tasks were found. Mice C57BL/6J showed good learning ability and preservation of memory traces tested 10 days after performance in a simplified version of Morris water maze. Mice BALB/c learned the task but, virtually, no long-term memory traces were revealed, whereas DBA/2J demonstrated poor learning. The effect of nootropic drug Noopept (GVS-111, N-phenil-acetyl-L-prolylglycin ethyl ether) was shown to be genotype-dependent. Its administration (0.5 mg/kg i.p., 15 min before learning) improved the long-term memory in Morris test in BALB/c mice but failed to produce any improvement in C57BL/6J. The ability of mice for extrapolation of the direction of stimulus movement differently changed after Noopept injections: the proportion of correct task solutions increased in C57BL/6J and BALB/c mice, whereas the performance of DBA/2J did not change.


Anthrax: has the clinical milieu changed since 2001?
Since the anthrax attacks of 2001 (Amerithrax), several important improvements in the knowledge of Bacillus anthracis and the clinical condition it causes have occurred. While much remains to be known about the optimal management of anthrax patients, several approaches that were not widely utilized, available, or known in 2001 would be used in the treatment of critically ill anthrax patients in 2012.


Anti-obesity effects of Taif and Egyptian pomegranates: molecular study.
The present study investigated the anti-obesity effects of pomegranate (Punica granatum) juices from the two Saudi Arabian, Taif red, Taif white, and Egyptian pomegranates in high-fat diet (HFD)-induced obese rats. Administrating any of the used juices decreased the body weight gain, food consumption, and serum levels of lipid, leptin, and glucose, while it increased serum insulin level. Histologically, all types of juices decreased the number and size of lipid droplets in hepatocytes compared to the obese, non-treated animals. All juices types upregulated the hepatic mRNA expression of hormone-sensitive lipase, pyruvate kinase, and adiponectin in obese rats; the genes were all suppressed by HFD feeding. Additionally, the expression of fatty acid synthase, sterol regulatory element-binding protein-1c, and acetyl-CoA carboxylase1 was also upregulated by all types of juices. Conversely, ghrelin mRNA expression was downregulated by all used juices' types. These findings demonstrate that all types of tested juices protect against the HFD-induced obesity in rats.


[The history of the speckled monster].
It demolished 3 empires, killed princess and peasants indifferently, blinded its victims and scarred them for life, changed the outcome of military conflicts and eventually induced the discovery of the vaccination technique. Although conquered in the late seventies of the 20th century, the spirit of "the speckled monster"--smallpox as it was called due to its coetaneous manifestation and high death rate, still roam the earth as a bioterrorist threat. From China to Turkey, from England to the U.S.A., smallpox plague history traverses nations and physicians. This paper discusses the history of the disease and brings forward some of the less famous characters who contributed to the eradication of smallpox.


From time-resolved atomic-scale imaging of individual donors to their cooperative dynamics.
The key elements in the steady miniaturization process of cutting-edge semiconductor devices are the understanding and controlling of charge dynamics on the atomic scale. In detail, we address the study of charging processes of individual doping atoms and, especially, the interaction of those atoms with their surroundings. We use pulsed optical excitation in combination with scanning tunneling microscopy at the n-doped gallium arsenide [GaAs(110)] surface to investigate single donor dynamics within a nanoscaled, localized space charge region. Tuning the tunnel rate can drive the system into nonequilibrium conditions, allowing distinction between the decay of optically induced free charge carriers and the decay of donor charge states. The latter process is atomically resolved and discussed with respect to donor-level binding energies and local donor configurations.


Horizontal visibility graph transfer entropy (HVG-TE): A novel metric to characterize directed connectivity in large-scale brain networks.
We propose a new measure, horizontal visibility graph transfer entropy (HVG-TE), to estimate the direction of information flow between pairs of time series. HVG-TE quantifies the transfer entropy between the degree sequences of horizontal visibility graphs derived from original time series. Twenty-one Rössler attractors unidirectionally coupled in the posterior-to-anterior direction were used to simulate 21-channel Electroencephalography (EEG) brain networks and validate the performance of the HVG-TE. We showed that the HVG-TE is robust to different levels of coupling strengths between the coupled Rössler attractors, a wide range of time delays, different sample sizes, the effects of noise and linear mixing, and the choice of reference for EEG data. We also applied HVG-TE to EEG data in 20 healthy controls and compared its performance to a recently introduces phase-based TE measure (PTE). We found that compared with PTE, HVG-TE consistently detected stronger posterior-to-anterior information flow patterns in the alpha-band (8-13Hz) EEG brain networks for three different references. Moreover, in contrast to PTE, HVG-TE does not require an assumption on the periodicity of input signals, therefore it can be more widely applicable, even for non-periodic signals. This study shows that the HVG-TE is a directed connectivity measure to characterise the direction of information flow in large-scale brain networks.


Diversity, prevalence, and expression of cyanase genes (cynS) in planktonic marine microorganisms.
Cyanate is utilized by many microbes as an organic nitrogen source. The key enzyme for cyanate metabolism is cyanase, converting cyanate to ammonium and carbon dioxide. Although the cyanase gene cynS has been identified in many species, the diversity, prevalence, and expression of cynS in marine microbial communities remains poorly understood. Here, based on the full-length cDNA sequence of a dinoflagellate cynS and 260 homologs across the tree of life, we extend the conserved nature of cyanases by the identification of additional ultra-conserved residues as part of the modeled holoenzyme structure. Our phylogenetic analysis showed that horizontal gene transfer of cynS appears to be more prominent than previously reported for bacteria, archaea, chlorophytes, and metazoans. Quantitative analyses of marine planktonic metagenomes revealed that cynS is as prevalent as ureC (urease subunit alpha), suggesting that cyanate plays an important role in nitrogen metabolism of marine microbes. Highly abundant cynS transcripts from phytoplankton and nitrite-oxidizing bacteria identified in global ocean metatranscriptomes indicate that cyanases potentially occupy a key position in the marine nitrogen cycle by facilitating photosynthetic assimilation of organic N and its remineralisation to NO3 by the activity of nitrifying bacteria.


Regulation of allergic reactions by aerobic Corynebacterium equi extract, CEF. II. Inhibition of Heterologous PCA and antigen-induced histamine release in rats.
A water-soluble fraction (CEF) obtained from Corynebacterium equi was administered intradermally or intravenously into Sprague-Dawley rats. Passive cutaneous anaphylaxis (PCA) was elicited in these rats along with the controls by sensitization with mouse anti-DNP serum and challenge with the corresponding antigen. PCA reactions were markedly inhibited by the pretreatments of the rats with CEF. Similar treatments of the animals 2-4h after the sensitization did not inhibit PCA. Inhibitory activity of CEF in the pretreated animals was shown to be dose-dependent. Incubation of rat peritoneal mast cells with CEF effectively blocked the binding of murine IgE antibodies to the cells as evidenced by the failure of the treated cells to bind the antibodies. Furthermore, antigen-induced histamine release from rat mast cells, which were sensitized with murine IgE antibodies, was reduced significantly by CEF treatment of the cells prior to the sensitization. Results of this study indicated that CEF inhibits the PCA in rats, presumably by blocking the binding of heterocytotropic antibodies to Fc receptor of mast cells.


Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance.
The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.


Mismatch repair deficiency and clinical implications in prostate cancer.
Despite recent therapeutic advances, castration-resistant prostate cancer (CRPC) remains a lethal disease and novel therapies are needed. Precision oncology provides an avenue for developing effective tailored approaches for treating malignancies based on a tumor's molecular profile. Indeed, the presence of mismatch repair deficiency (MMRd) has proven to be an important predictive biomarker for response to immune checkpoint blockade across multiple tumor types, including prostate cancer, and represents a major precision oncology success story. The mismatch repair (MMR) system is integral to maintaining genomic fidelity during cellular replication. Cancers with deficiencies in this system accumulate high numbers of mutations and express many neoantigens that may be recognized by the immune system. The checkpoint inhibitor pembrolizumab has recently been approved for all cancers that are MMR deficient, and several retrospective series have specifically shown that pembrolizumab is effective in MMRd prostate cancer. Although the prevalence of MMRd in CRPC is low (approximately 3%-5% of cases), this is an important subset of men that require a unique therapeutic approach. This review will focus on MMRd in prostate cancer, highlighting the clinical implications, role of immunotherapy, and areas of future research.


Quantification of coral sperm collected during a synchronous spawning event.
Most studies of coral reproductive biology to date have focused on oocyte numbers and sizes. Only one (ex situ) study has enumerated sperm numbers, even though these data have multiple potential applications. We quantified total coral sperm and eggs per gamete bundle collected from six species in situ during a synchronous spawning event in Singapore. Egg-sperm bundles were captured midwater as they floated towards the surface after being released by the colony. For each sample, a semi-transparent soft plastic bottle was squeezed and released to create a small suction force that was used to 'catch' the bundles. This technique provided several advantages over traditional methods, including low cost, ease of use, no diving prior to the night of collection needed, and the ability to target specific areas of the colony. The six species sampled were Echinophyllia aspera, Favites abdita, F. chinensis, Merulina ampliata, M. scabricula and Platygyra pini. The mean number of sperm packaged within one egg-sperm bundle ranged from 2.04 × 10(6) to 1.93 × 10(7). The mean number of eggs per egg-sperm bundle ranged from 26.67 (SE ± 3.27) to 85.33 (SE ± 17.79). These data are critical for fertilisation success models, but the collection technique described could also be applied to studies requiring in situ spawning data at the polyp level.


[Identification and treatment of missing data].
Missing data plagues almost all surveys and researches. The occurrence of missing data will cause losses of original sample information and undermine the validity of the research results to some extents, so researchers should attach great importance to this problem. In this article, we introduced 3 kinds of missingness mechanism, namely missing completely at random, missing at random, and not missing at random. We summarized some common approaches to deal with missing data, including deletion, weighting approach, imputation and parameter likelihood method. Since these methods had its pros and cons, we should carefully select the proper way to handle missing data according to the missingness mechanism.


Indicator displacement assays inside live cells.
The macrocycle p-sulfonatocalix[4]arene (CX4) and the fluorescent dye lucigenin (LCG) form a stable host-guest complex, in which the dye fluorescence is quenched. Incubation of live V79 and CHO cells with the CX4/LCG chemosensing ensemble resulted in its spontaneous uptake. Subsequent addition of choline, acetylcholine, or protamine, which have a high affinity for CX4 and are capable of entering cells, resulted in a fluorescence switch-on response. This can be traced to the displacement of LCG from CX4 by the analytes. The results establish the principal functionality of indicator displacement assays with synthetic receptors for the detection of the uptake of bioorganic analytes by live cells.


Cognitive mapping and elderly adults: verbal and location memory for urban landmarks.
This study provides a real-world memory task that extends the ecological validity of previous research on aging and spatial memory. Elderly individuals were found to have less accurate verbal recall of urban landmarks and location memory for landmarks than younger adults. In addition to these quantitative differences in environmental cognition, qualitative aspects of the data were explored. In order to explain the poorer memory performance of elderly adults, participants' use of a geographically based, organizational mnemonic was examined. Furthermore, discriminant analysis revealed that the elderly relied more than younger adults on certain building attributes for memory of urban landmarks. These building attributes include: high public use, high symbolic significance, naturalness of surroundings, direct access to streets, and unique architectural style.


Dysregulation of miR-155 Expression in Professional Mixed Martial Arts (MMA) Fighters.
Psychological and physical stress can induce dysregulation of gene expression via changes in DNA methylation and microRNA (miRNA) expression. Such epigenetic modifications are yet to be investigated in professional Mixed Martial Arts (MMA) fighters subject to highly stressful training involving repetitive head impacts. This study examined differences in DNA methylation and miRNA expression in elite MMA fighters compared to active controls. Global methylation differences between groups were assessed via a LINE-1 assay. At the same time, PCR arrays were used to estimate differential expression in samples of 21 fighters and 15 controls for 192 different miRNAs associated with inflammatory diseases. An Independent-Samples t-Test found no significant difference in LINE-1 methylation between groups. However, an Independent-Samples Mann-Whitney U Test revealed a significant upregulation in the expression of miR-155 in MMA fighter plasma. Since miR-155 has been recognized as an important regulator of neuroinflammation, this dysregulation suggests a possible epigenetic mechanism responsible for chronic inflammation associated with professional-level MMA training. Consistent with other published works, this study highlights the potential of miR-155 not only as a biomarker for monitoring long-term health risks linked to head trauma but also as a target to remediate the impact of chronic neuroinflammation.


Blast Wave Exposure to the Extremities Causes Endothelial Activation and Damage.
Extremity injury is a significant burden to those injured in explosive incidents and local ischaemia can result in poor functionality in salvaged limbs. This study examined whether blast injury to a limb resulted in a change in endothelial phenotype leading to changes to the surrounding tissue.The hind limbs of terminally anaesthetized rabbits were subjected to one of four blast exposures (high, medium, low, or no blast). Blood samples were analyzed for circulating endothelial cells pre-injury and at 1, 6, and 11 h postinjury as well as analysis for endothelial activation pre-injury and at 1, 6, and 12 h postinjury. Post-mortem tissue (12 h post-injury) was analysed for both protein and mRNA expression and also for histopathology. The high blast group had significantly elevated levels of circulating endothelial cells 6 h postinjury. This group also had significantly elevated tissue mRNA expression of IL-6, E-selection, TNF-α, HIF-1, thrombomodulin, and PDGF. There was a significant correlation between blast dose and the degree of tissue pathology (hemorrhage, neutrophil infiltrate, and oedema) with the worst scores in the high blast group. This study has demonstrated that blast injury can activate the endothelium and in some cases cause damage that in turn leads to pathological changes in the surrounding tissue. For the casualty injured by an explosion the damaging effects of hemorrhage and shock could be exacerbated by blast injury and vice versa so that even low levels of blast become damaging, all of which could affect tissue functionality and long-term outcomes.


IL-15 Harnesses Pro-inflammatory Function of TEMRA CD8 in Kidney-Transplant Recipients.
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM). IL-15 induces antiapoptotic signals and promotes proliferation dependent of PI3K/Akt, MAPK, and ERK pathways. Without ex vivo stimulation, TEMRA cells are metabolically more active than naive and EM, as shown by their high ATP reservoir and a high expression of genes involved in glycolysis, glutaminolysis, and the Pentose Phosphate Pathway. Upon stimulation, TEMRA adapt their metabolism by sustaining an increased mitochondrial respiration and glycolysis. Finally, we show that the inhibition of glycolysis is highly effective in preventing endothelial inflammation induced by TEMRA from KT recipients. Together, our findings highlight the metabolic fitness that tightly regulates the immune function of TEMRA in physiological and pathogenic situations.


[Synthesis and characterizations of poly (ethylene glycol)-block-poly (glutamate)].
Amine-terminated poly (ethylene glycol) (PEG) was prepared by two steps. Firstly, potassium naphthalene was added to a solution of methoxypolyethylene glycol 5,000 in benzene until the solution maintains green in half of an hour, then excess tosylchloride was introduced; secondly, the conversion of the tosylate into an amine was carried out by Gabriel synthesis. The block copolymer poly (ethylene glycol)-co-poly (gamma-benzyl L-glutamate ) could be obtained by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxy anhydride with amine-terminated PEG as macroinitiator. And the benzyl group could be removed by sodium hydroxide. The product structure was characterized by IR, 1HNMR, GPC. The cisplatin-loaded micelle was observed by transmission electron microscope (TEM). And the block copolymer is expected to be useful as functional materials including carrier systems in drug controlled delivery applications.


A new method for the gradient-based optimization of molecular complexes.
We present a novel method for the local optimization of molecular complexes. This new approach is especially suited for usage in molecular docking. In molecular modeling, molecules are often described employing a compact representation to reduce the number of degrees of freedom. This compact representation is realized by fixing bond lengths and angles while permitting changes in translation, orientation, and selected dihedral angles. Gradient-based energy minimization of molecular complexes using this representation suffers from well-known singularities arising during the optimization process. We suggest an approach new in the field of structure optimization that allows to employ gradient-based optimization algorithms for such a compact representation. We propose to use exponential mapping to define the molecular orientation which facilitates calculating the orientational gradient. To avoid singularities of this parametrization, the local minimization algorithm is modified to change efficiently the orientational parameters while preserving the molecular orientation, i.e. we perform well-defined jumps on the objective function. Our approach is applicable to continuous, but not necessarily differentiable objective functions. We evaluated our new method by optimizing several ligands with an increasing number of internal degrees of freedom in the presence of large receptors. In comparison to the method of Solis and Wets in the challenging case of a non-differentiable scoring function, our proposed method leads to substantially improved results in all test cases, i.e. we obtain better scores in fewer steps for all complexes.


Introducing Ratiometric Fluorescence to MnO2 Nanosheet-Based Biosensing: A Simple, Label-Free Ratiometric Fluorescent Sensor Programmed by Cascade Logic Circuit for Ultrasensitive GSH Detection.
Glutathione (GSH) plays crucial roles in various biological functions, the level alterations of which have been linked to varieties of diseases. Herein, we for the first time expanded the application of oxidase-like property of MnO2 nanosheet (MnO2 NS) to fluorescent substrates of peroxidase. Different from previously reported fluorescent quenching phenomena, we found that MnO2 NS could not only largely quench the fluorescence of highly fluorescent Scopoletin (SC) but also surprisingly enhance that of nonfluorescent Amplex Red (AR) via oxidation reaction. If MnO2 NS is premixed with GSH, it will be reduced to Mn2+ and lose the oxidase-like property, accompanied by subsequent increase in SC's fluorescence and decrease in AR's. On the basis of the above mechanism, we construct the first MnO2 NS-based ratiometric fluorescent sensor for ultrasensitive and selective detection of GSH. Notably, this ratiometric sensor is programmed by the cascade logic circuit (an INHIBIT gate cascade with a 1 to 2 decoder). And a linear relationship between ratiometric fluorescent intensities of the two substrates and logarithmic values of GSH's concentrations is obtained. The detection limit of GSH is as low as 6.7 nM, which is much lower than previous ratiometric fluorescent sensors, and the lowest MnO2 NS-based fluorescent GSH sensor reported so far. Furthermore, this sensor is simple, label-free, and low-cost; it also presents excellent applicability in human serum samples.


Deafness among combat soldiers exposed to noise trauma.
To investigate the pattern of deafness in combat soldiers exposed to noise trauma. Patients were assessed clinically and audiologically. Pure tone audiograms were done on admission, after two weeks and after one month. ENT department, Military Hospital, Army Headquarters, Colombo 2. 724 injured soldiers from the combat zone who complained of hearing impairment. The pattern of deafness depends on type of weapon, the position of the body on the ground, proximity to the weapon and (4) whether wearing hearing protectors or not. Adequate screening of soldiers before enlistment and regular audiological assessment are necessary for prevention and identification of hearing loss. Adequate hearing protection, early treatment of the injured and avoidance of further exposure to noise will prevent permanent disability.


Back to the roots? Dual cannulation strategy for ambulatory ECMO in adolescent lung transplant candidates: An alternative?
Bridging critically ill pediatric patients to lung transplantation still remains a major challenge. Although still controversial, within the last 5 years, ECMO has been increasingly used as a bridge to lung transplantation concept in adult and pediatric patients with acceptable outcomes. The outstanding developments in the field of extracorporeal devices and the introduction of awake ECMO concepts with the avoidance of mechanical ventilation have led to a real paradigm shift in the ICU management of pretransplant candidates with severe respiratory failure. Therefore, ECMO is no longer seen as a contraindication for lung transplantation at least at our center. Nevertheless, how to bridge these patients on ECMO still remains controversial. Thus, we introduced an ambulatory ECMO approach in adolescent lung transplant candidates with acute respiratory failure using a dual cannulation strategy and hereby present first results from this procedure.


Reduction in morning blood pressure is a key factor for ameliorating urinary albumin excretion in patients with morning hypertension irrespective of treatment regimen.
The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.


High performance liquid chromatography and pharmacokinetics of the non-steroidal anti-inflammatory drug oxindanac in calves.
A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.375 to 62.5 micrograms/ml were 90.2-107.8% with interassay coefficients of variation of 2.1-22.3%. The limit of detection was estimated as 0.10 micrograms/ml and the limit of quantification calculated to be 0.24 micrograms/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t1/2 was long (t1/2 21.2 h after i.v. injection) and absorption was rapid (t1/2a 0.072 h) and complete (F > 100%) following i.m. administration. Bioavailability was incomplete (F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed two absorption phases (t1/2's 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB2 production, with mean Emax values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.o. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36-48 h.


Characteristics of immobilized lipase-catalyzed hydrolysis of olive oil of high concentration in reverse phase system.
Candida rugosa lipase immobilized by adsorption on swollen Sephadex LH-20 could almost completely hydrolyze 60% (v/v) olive oil in isooctane. Kinetic analysis of the lipase-catalyzed hydrolysis reaction was found to be possible in this system. Amount of fatty acids produced was linearly proportional to the enzyme concentration of 720 microg/g wet gel. The specific enzyme activity was 217 units/mg protein at 60% (v/v) olive oil concentration. When the initial rate is plotted versus concentration of olive oil, this system did not follow Michaelis-Menten kinetics. Maximum activity was obtained at pH 7, but optimum temperature shifted towards higher one with the increase of olive oil concentration. Among the various chemical compounds tested, Hg(2+) and Fe(2+) inhibited the lipase seriously. As the concentration of olive oil increased, the rate of the hydrolysis also increased, but degree of the hydrolysis was observed to decrease. The supply of water from the inside of the gel to the surface of the gel was the main factor for the control of the rate of hydrolysis in batch hydrolysis. The immobilized lipase was used to hydrolyze olive oil two times. Achievement of chemical equilibrium took a longer time with the addition of water and the degree of hydrolysis decreased in the second consecutive trial. After the second hydrolysis trial, the gels were regenerated in a packed column first by eluting out both residual fatty acids around the gel particles and the accumulated glycerol with ethanol and then with 0.05 M phosphate buffer, pH 7. The immobilized lipase on the regenerated gel showed the same hydrolysis activity as the original one.


Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions.
To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy. Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed. In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically. The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.


[Preliminary observation of galvanic vestibular stimulation-vestibular evoked myogenic potentials in healthy young people].
Objective: To introduce the method of galvanic vestibular stimulation-vestibular evoked myogenic potentials (GVS-VEMP) as well as to observe and analyze the parameters and elicited rate of GVS-cVEMP and GVS-oVEMP in healthy young people in China. Methods: Twenty six normal young subjects were recruited for conventional examinations of GVS-VEMP. The subjects were 21-37 years old, average age was (25.8±3.7) years old, including 13 males and 13 females. The galvanic stimulation intensity of 3 mA/1 ms was used to evoke cVEMP and oVEMP on the sternocleidomastoid and inferior extraocular muscles respectively, and the intensity of stimulus was decreased until the response disappeared, the threshold, latency, amplitude, interval phase and interaural amplitude ratio(IAR) were calculated. SPSS18.0 software was used for statistical analysis. Results: All subjects were elicited normal GVS-cVEMP and GVS-oVEMP under 3 mA/1 ms, the elicited rate was 100%. The threshold of GVS-cVEMP was (1.18±0.47) mA, p1 latency was (10.43±1.54) ms, n1 latency was (17.91±1.20) ms, the amplitude was (102.47±56.77) uV and IAR was (0.26±0.20). The threshold of GVS-oVEMP was (1.12±0.50) mA, n1 latency was (8.46±1.05) ms, p1 latency was (11.83±1.27) ms, the amplitude was (9.12±6.82) uV and IAR was (0.25±0.20). In terms of gender and lateral comparison, only the GVS-oVEMP amplitude was higher for male than for female, which had significant statistical difference (P<0.05), and there was no statistical difference in the other parameters between GVS-cVEMP and GVS-oVEMP. Conclusion: GVS-cVEMP and GVS-oVEMP could be elicited in healthy youth population, and the parameters could provide reference for subsequent vestibular function evaluation.


EFFICACY AND SAFETY OF A TREAT-AND-EXTEND REGIMEN WITH AFLIBERCEPT IN TREATMENT-NAIVE PATIENTS WITH TYPE 3 NEOVASCULARIZATION: A 52-Week, Single-Arm, Multicenter Trial.
To evaluate 52-week efficacy and safety of a treat-and-extend regimen of intravitreal aflibercept 2 mg on treatment-naive Type 3 neovascularization lesions. Phase IV, prospective, open-label, single-arm, multicenter trial including patients with untreated Stage I/II Type 3 neovascularization lesions and baseline best-corrected visual acuity between 78 and 23 Early Treatment Diabetic Retinopathy Study letters. Primary endpoint: mean change in best-corrected visual acuity from baseline at 52 weeks. Thirty-two eyes from 32 patients were included (mean ± SD age: 78.2 ± 7.7 years, 68.8% females, baseline best-corrected visual acuity: 57.9 ± 15.4 [Snellen fraction 20/70]). Best-corrected visual acuity increased by 10.5 ± 15.9 Early Treatment Diabetic Retinopathy Study letters at Week 52 (P = 0.0001). The mean foveal and choroidal thickness decreased by 129.1 ± 80.1 µm (P < 0.0001) and 64.3 ± 96.5 (P = 0.0001), respectively. The proportion of patients with intraretinal/subretinal fluid decreased from 28 (87.5%) at baseline to 3 (11.5%) at Week 52 (P < 0.0001). Pigment epithelial detachment and lesion area showed nonsignificant changes over 52 weeks. The mean number of injections was 8.0 ± 2.0. Seven (21.9%) patients experienced treatment-related adverse events and two (6.3%) experienced serious adverse events; one (3.1%) ocular serious adverse event requiring treatment withdrawal, endophthalmitis, and one (3.1%) nonocular spontaneously resolved serious adverse event, palpitations. One (3.1%) patient experienced an APTC ATE: nonfatal stroke not related to trial treatment. A treat-and-extend regimen of aflibercept improves visual acuity and retinal edema in eyes with Type 3 neovascularization over 52 weeks with good tolerability.


[The management of bleeding pseudoaneurysms in patients with severe acute pancreatitis].
To report the experience in diagnosis and management of bleeding pseudoaneurysms associated with severe acute pancreatitis (SAP). The medical records of 12 patients with bleeding pseudoaneurysms associated with SAP treated between October 1990 and October 2006 were retrospectively reviewed. The etiologies of the 12 patients were gallstones in 6 patients, hyperlipidemia in 3 patients, hyperparathyroidism in 1 patient and the other 2 patients had no definitive causes. Abdominal computed tomography revealed bleeding pseudoaneurysms in 6 of 9 patients. Angiography determined correct diagnosis in 12 patients (12/12). The most involved vessels were peripancreatic arteries. Eight patients were managed by trans-catheter arterial embolization (TAE) as "one point" (a proximal point of the pseudo-aneurysm). Two patients were treated by TAE as "two points" (both distal and proximal to the pseudo-aneurysm). The last two cases were treated by surgery as suture and ligation. Four of the "one point" TAE patients were re-bleeding 4 to 7 days later, and 2 of them were treated with surgery, the other 2 patients were controlled with "two points" TAE. Three patients were died of infection and multiple organ dysfunction syndromes. Overall mortality rate was 25% (3/12). Angiography is the main diagnostic methods for bleeding pseudoaneurysms in SAP patients. "Two points" embolization and emergency surgery are an effective treatment options in these patients.


Surface rearrangement of water-immersed hydrophobic solids by gaseous nanobubbles.
Interactions of gaseous (ambient) nanobubbles (10-100 nm diameter) with different hydrophobic materials-Teflon, polystyrene, paraffin, and basal plane highly ordered pyrolytic graphite (HOPG)-are studied by AFM in situ and ex situ. Exactly identical surface locations are examined before and after exposure to ambient gas nanobubbles in deionized water and compared for nanomorphological changes. While freely flooded/immersed surfaces, regularly occupied by nanobubbles, do not exhibit resolvable alterations, significant surface rearrangement is found on whole flooded area after mild pressure drop (10 kPa) applied on the solid-liquid interface. Nanopattern and its characteristic dimension appear to be material specific and solely reflect surface-nanobubble interaction. Mild, nonswelling, noncorrosive conditions (20 °C, deionized water) prevent intervention of chemical reaction and high-energy-demanding processes. Experimental results, in accordance with the presented model, indicate that the mild pressure drop triggers expansion of pinned nanobubbles, imposing local tensile stress on the solid surface. Consequently, nanobubbles should be considered as large-area nanoscale patterning elements.


Envelope frequency following responses are stronger for high-pass than low-pass filtered vowels.
To assess hearing in response to speech, the envelope frequency following response (FFR) can be observed at the fundamental frequency of a vowel stimulus and its harmonics. FFRs are complex non-linear phenomena, which require better understanding for allowing robust inferences on the assessment of hearing and hearing aid fitting. To evaluate the effect of stimulus bandwidth on FFR detection rates using filtered vowel stimuli with equal sound levels. FFRs were collected whilst presenting repeated vowels (in consonant-vowel-consonant format) filtered into different bandwidths. Eighty stimuli per word were presented at 70 dB SPL LAeq through insert earphones with an inter-stimulus interval of 1 s. Responses were detected using frequency-domain Hotelling's T2 (HT2) tests for individual multiples of the fundamental frequency (F0) and for combinations of F0 multiples. A total of 11 native English-speaking subjects with normal hearing thresholds. Average detection rates are highest (69%) with stimuli high-pass filtered >1000 Hz, and significantly lower for low-pass filtered stimuli (40%). High-pass filtered vowels therefore appear to elicit stronger FFRs than low-pass filtered vowels at the same dB SPL LAeq. For testing hearing using band-limited speech, filtering effects (due to hearing loss, hearing aid setting or stimulus choice) on responses must be considered.


Multimodal early-life stress induces biological changes associated to psychopathologies.
Evidences suggest the contributive role of early-life stress (ELS) to affective and anxiety disorders. Chronic exposure to the same stressor may generate habituation, while the exposure to different and repeated stressors gradually promotes maladaptive plasticity. Therefore, to further understand the effects of heterotypic stressors during early life period, male Wistar rat pups (P1-P21) were exposed to Multimodal ELS paradigm. Results indicate pups did not habituate to multimodal ELS and neonates respond to both physical and psychogenic stressors. Adult rats that underwent ELS protocol showed significant lower sucrose intake, decreased latency to immobility in the forced swim test and increased latency to light compartment in the light-dark test when compared to control group. Although it has been shown that ELS-induced changes in hippocampus can be used as biomarkers, multimodal ELS did not significantly alter BDNF, Tyrosine Kinase B (TrkB) receptor expression or neurogenesis in the hippocampus. Taken together, these findings indicate that multimodal ELS protocol can be an interesting experimental model for understanding long-term psychiatric disorders associated with stress. Indeed, our data with neurogenesis, BDNF and TrkB, and conflicting data from the literature, suggest that additional studies on synaptic plasticity/intracellular cascades would help to detect the underlying mechanisms.


The impact of nitrogen gas flushing on the stability of seasonings: volatile compounds and sensory perception of cheese & onion seasoned potato crisps.
The impact of natural cheese and onion seasoning on the sensory perception and shelf life stability of potato crisps was studied. This study was carried out to evaluate the impact of nitrogen (N2) gas flushing on the shelf-life stability and sensory attributes of cheese & onion seasoned potato crisps. Markers of lipid oxidation and flavour volatile compounds were evaluated in sliced, unwashed, batch fried potato crisps during accelerated storage at 45 °C for 10 weeks. Volatile flavour compounds were evaluated by headspace gas analysis using solid phase microextraction (SPME) GC-MS and correlated with sensory perception. Gas flushing significantly increases the shelf life of both unsalted and cheese & onion seasoned potato crisps in terms of the stability of volatile compounds and sensory perception. Further to this, the addition of the cheese & onion seasoning increased the shelf life of the base potato crisp; this is proposed to be explained by the antioxidant properties of milk proteins in the seasoning. Sensory evaluation indicated that the key negative sensory attributes reported were rancidity and stale attributes, which were correlated to the progression of lipid oxidation and loss of flavour over storage time irrespective of the packaging environment (with/without gas flushing).


Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells.
Inhibition of complex I (CI) of the mitochondrial respiratory chain by BAY 87-2243 ('BAY') triggers death of BRAFV600E melanoma cell lines and inhibits in vivo tumor growth. Here we studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential (Δψ), increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. These effects were paralleled by increased opening of the mitochondrial permeability transition pore (mPTP) and stimulation of autophagosome formation and mitophagy. BAY-induced cell death was not due to glucose shortage and inhibited by the antioxidant α-tocopherol and the mPTP inhibitor cyclosporin A. Tumor necrosis factor receptor-associated protein 1 (TRAP1) overexpression in BAY-treated cells lowered ROS levels and inhibited mPTP opening and cell death, whereas the latter was potentiated by TRAP1 knockdown. Knockdown of autophagy-related 5 (ATG5) inhibited the BAY-stimulated autophagosome formation, cellular ROS increase and cell death. Knockdown of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) inhibited the BAY-induced Δψ depolarization, mitophagy stimulation, ROS increase and cell death. Dynamin-related protein 1 (Drp1) knockdown induced mitochondrial filamentation and inhibited BAY-induced cell death. The latter was insensitive to the pancaspase inhibitor z-VAD-FMK, but reduced by necroptosis inhibitors (necrostatin-1, necrostatin-1s)) and knockdown of key necroptosis proteins (receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and mixed lineage kinase domain-like (MLKL)). BAY-induced cell death was also reduced by the ferroptosis inhibitor ferrostatin-1 and overexpression of the ferroptosis-inhibiting protein glutathione peroxidase 4 (GPX4). This overexpression also inhibited the BAY-induced ROS increase and lipid peroxidation. Conversely, GPX4 knockdown potentiated BAY-induced cell death. We propose a chain of events in which: (i) CI inhibition induces mPTP opening and Δψ depolarization, that (ii) stimulate autophagosome formation, mitophagy and an associated ROS increase, leading to (iii) activation of combined necroptotic/ferroptotic cell death.


Cardiovascular risk factors and ultrasound evaluation of intima-media thickness at common carotids, carotid bulbs, and femoral and abdominal aorta arteries in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a tendency for obesity, high insulin, and high 24-h blood pressure levels has been reported in children and adolescents. Increased intima-media thickness (IMT) is considered a measure of subclinical atherosclerosis and a predictor of myocardial infarction and stroke. The objective of the study was to evaluate glucose metabolism, lipid profile, IMT of the abdominal aorta, right and left common carotids, carotid bulbs, and common femoral arteries in adult CAH patients. Nineteen (10 females, nine males; 28 +/- 3.5 yr) patients (12 salt wasting and seven simple virilizing) and 19 (10 females, nine males) healthy subjects matched for anthropometric parameters (age, sex, body mass index, smoking habit, waist to hip ratio, and blood pressure). Glucose metabolism was studied using the oral glucose tolerance test and the homeostasis model assessment-insulin resistance. The echo-Doppler was used for arterial ultrasound. 17-Hydroxyprogesterone, androstenedione, testosterone, ACTH, plasma renin activity, total and high-density lipoprotein cholesterol, and triglycerides were measured. CAH patients had significantly higher fasting plasma insulin (11.6 +/- 6.20 microU/ml vs 5.18 +/- 2.4 microU/ml; P < 0.0001) and homeostasis model assessment-insulin resistance than controls (2.46 +/- 1.92 vs 1.12 +/- 0.58; P = 0.0033). IMT of the studied arteries was higher in CAH patients than controls. There was no correlation between IMT and cumulative glucocorticoid doses and androgen levels. A reduced insulin sensitivity and increased IMT were demonstrated in adults with CAH, who consequently need a follow-up for cardiovascular risk.


Borderline epithelial tumors of the ovary: ovarian intraepithelial neoplasia.
Although the concept of low malignant potential and/or borderline malignancy of some epithelial ovarian tumors was endorsed by the World Health Organization in 1973, uncertainty exists regarding the biologic behavior aspects of these lesions and this may account for the discrepancy in the 5-year survival figures reported for patients afflicted with these malignancies (76-95 per cent). We have reviewed the clinicopathologic aspects of 26 cases of borderline epithelial ovarian tumors and searched the literature. Based on our analysis, we have concluded that: 1) rupture of the cyst at surgery did not affect the patient's outcome but positive peritoneal fluid cytology did. 2) The term borderline should be replaced by ovarian intraepithelial neoplasia or preinvasive carcinoma and should solely be used in patients with stage I disease. 3) There is no justification for adjuvant therapy in adequately staged and surgically treated stage Ia and Ib disease. 4) Patients with stage II or more disease and those with positive peritoneal fluid cytology should be treated as aggressively as all other invasive, well-differentiated, epithelial ovarian tumors. 5) Our observation in cases of epithelial ovarian tumor cells grown on an extracellular matrix tends to indicate that parameters other than morphology may aid in assessing the invasive potential of these malignancies.


Electrocardiogram parameters for predicting future arrhythmia in patients with stable chronic obstructive pulmonary disease.
Arrhythmia is one of the common comorbidities in chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate arrhythmia predictors by using ECG in non-hypoxemic patients with stable COPD in outpatient clinics. Fifty patients with COPD and 21 age-sex matched healthy controls were enrolled. Exclusion criteria were having history of exacerbation in the last two months, any cardiac symptoms, comorbidities, hypoxemia for COPD patients, and additionally, history of smoking for healthy controls. Twelve-lead ECGs were obtained from all patients. Mean was 55 ± 4 year in all participants. Median Medical Research Council (MRC) score of COPD patients was 2 and median value of FEV1 was 49%. Median heart rate of COPD patients was 77/min with normal sinus rhythm, significantly faster than healthy controls. P-min, QTcmin, Tp-edisp, Tp-e/QT were significantly different from the control group. In patients with COPD, whilst significant correlations between pulmonary functions and Qtcmin, Qtc-max, p-min were found, there were no significant differences between groups of spirometric stages. Smoking and mMRC dyspnea scale were not correlated with ECG findings. This study showed that non-hypoxemic COPD patients with decreased pulmonary functions, without cardiac symptoms and comorbidities, could have risks for atrial, ventricular arrhythmias regardless of dyspnea, smoking.


DUB3 and USP7 de-ubiquitinating enzymes control replication inhibitor Geminin: molecular characterization and associations with breast cancer.
Correct control of DNA replication is crucial to maintain genomic stability in dividing cells. Inappropriate re-licensing of replicated origins is associated with chromosomal instability (CIN), a hallmark of cancer progression that at the same time provides potential opportunities for therapeutic intervention. Geminin is a critical inhibitor of the DNA replication licensing factor Cdt1. To properly achieve its functions, Geminin levels are tightly regulated through the cell cycle by ubiquitin-dependent proteasomal degradation, but the de-ubiquitinating enzymes (DUBs) involved had not been identified. Here we report that DUB3 and USP7 control human Geminin. Overexpression of either DUB3 or USP7 increases Geminin levels through reduced ubiquitination. Conversely, depletion of DUB3 or USP7 reduces Geminin levels, and DUB3 knockdown increases re-replication events, analogous to the effect of Geminin depletion. In exploring potential clinical implications, we found that USP7 and Geminin are strongly correlated in a cohort of invasive breast cancers (P<1.01E-08). As expected, Geminin expression is highly prognostic. Interestingly, we found a non-monotonic relationship between USP7 and breast cancer-specific survival, with both very low or high levels of USP7 associated with poor outcome, independent of estrogen receptor status. Altogether, our data identify DUB3 and USP7 as factors that regulate DNA replication by controlling Geminin protein stability, and suggest that USP7 may be involved in Geminin dysregulation during breast cancer progression.


Graphene-Wrapped MgO/Poly(vinyl alcohol) Composite Sheets: Dielectric and Electromagnetic Interference Shielding Properties at Elevated Temperatures.
Different amounts of graphene-wrapped magnesium oxide (G@MgO) powders are uniformly dispersed in poly(vinyl alcohol) (PVA) solution in different experiments to obtain solutions which are coagulated to obtain solid materials, which are then hot pressed at 413 K and 3 t of pressure to finally obtain 1 mm thick freestanding G@MgO/PVA composite sheets in which the constituents, namely, graphene and MgO (in the form of G@MgO), are the nanofillers in PVA matrix. During synthesis of G@MgO powder, MgO nanoparticles are in situ wrapped by the graphene nanosheets as revealed by electron microscopy. Uniformity of G@MgO dispersion in PVA was confirmed by secondary electron micrographs and the consistency in X-ray diffraction and Raman scattering data collected from different locations of the samples. Temperature (303-393 K) dependent complex permittivity of G@MgO/PVA composite sheets (including those prepared by casting) in low frequency (20 Hz to 2 MHz) and high frequency (i.e., X-band, 8.2-12.4 GHz) ranges are measured. In both frequency ranges, G@MgO/PVA composite sheets prepared by coagulation exhibited dielectric properties superior to those of PVA and G@MgO/PVA composite sheets prepared by casting. A strong interfacial polarization is observed in coagulated and as-cast G@MgO/PVA composite sheets. It is noticed from the calculated activation energies that conduction is the dominating mechanism for energy transfer in both composite sheets' cases, while it is predominating in coagulated composite sheets due to the better network formation of the fillers in the coagulated samples than in the cast composite samples. The electromagnetic interference shielding effectiveness (EMI SE) values in the X-band frequency range (i.e., 8.2-12.4 GHz) of the G@MgO/PVA composite sheets prepared by coagulation are more than those prepared by casting for a particular weight fraction of G@MgO. At 393 K, for a particular G@MgO/PVA composite sheet prepared by coagulation, an excellent EMI SE of ∼27.5 dB is measured. It is also experimentally elucidated that the absorption is the dominating mechanism for EMI SE in the prepared composite sheets.


Skip lesions in temporal arteritis.
Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.


Gaucher disease gene GBA functions in immune regulation.
Inherited deficiency of acid β-glucosidase (GCase) due to biallelic mutations in the GBA (glucosidase, β, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs. Clinical observations point to immune defects in GD beyond the accumulation of activated macrophages engorged with lysosomal glucosylceramide. Here, we show a plethora of immune cell aberrations in mice in which the GBA gene is deleted conditionally in hematopoietic stem cells (HSCs). The thymus exhibited the earliest and most striking alterations reminiscent of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes. These changes correlated strongly with disease severity. In contrast to the profound defects in the thymus, there were only limited cellular defects in peripheral lymphoid organs, mainly restricted to mice with severe disease. The cellular changes in GCase deficiency were accompanied by elevated T-helper (Th)1 and Th2 cytokines that also tracked with disease severity. Finally, the proliferation of GCase-deficient HSCs was inhibited significantly by both GL1 and Lyso-GL1, suggesting that the "supply" of early thymic progenitors from bone marrow may, in fact, be reduced in GBA deficiency. The results not only point to a fundamental role for GBA in immune regulation but also suggest that GBA mutations in GD may cause widespread immune dysregulation through the accumulation of substrates.


The cracked tooth conundrum: terminology, classification, diagnosis, and management.
To provide an overview of the clinical features, diagnosis, classification and management of cracked teeth which may be a diagnostic challenge in clinical practice. Cracks may initiate from coronal tooth structure or from within the root and affect healthy or root treated teeth. There are many terminologies and classifications in the literature for cracked teeth that can be as confusing as the array of clinical symptoms which are associated with this condition. The term "cracked tooth syndrome" is misleading as there are a range of symptoms that do not form a distinct and reliable pattern. Symptoms will vary with teeth that have healthy pulps, for teeth with inflamed or necrotic pulps, and for teeth that have been root treated. The American Association of Endodontists have classified five specific variations of cracked teeth; craze line, fractured cusp, cracked tooth, split tooth, and vertical root fracture. The importance of differentiating dentin, pulpal and periodontal pain for diagnosis and treatment for these specific entities will be elaborated. A decision flow chart indicating the treatment options available is presented.


The impact of excess heat events in Maricopa County, Arizona: 2000--2005.
Exposure to excess heat is preventable yet it is the primary weather-related cause of mortality in the United States. In the Southwest United States, high temperatures are common and indoor environments often have cooling devices. In summer 2005, Maricopa County, Arizona experienced a 182% increase in reported heat-related deaths in comparison to 2000--2004. We examined at-risk populations and excess mortality. We characterized heat-related deaths using descriptive and multivariate time-series analyses of county vital record data from June-September 2000--2005. Dose-response relationships for heat-related mortality and heat index were evaluated using linear and quadratic splines. From June-September, 2000--2005, 136 heat-related deaths (0.68 per 100,000) were reported; 49 (36%) occurred in 2005. In July 2005, a 14-day heat wave resulted in 28 (57%) reported deaths--a 102% increase in comparison to the same time period in 2000--2004. Decedent demographics in 2005 did not differ from previous years. The mean age of all 136 deaths was 56 years (range: 7-92 years). Of those with discernable reported injury locations, 62 (66%) were identified outdoors. Forty-eight (77%) decedents identified outdoors were < 5 years; conversely, 26 (82%) decedents who were found indoors were > or = 65 years. A 6% (95% CI: 1.00-1.13) increase in mortality risk was observed for each degree (F) increase in heat index. Excess heat impacted a younger population in Maricopa County and many deaths occurred outdoors. Consecutive days of heat exposure--even among a heat-acclimated population--can increase mortality risk. Public health response activities guided by locally obtained data will better target those at risk.


Group amplification in schools for the hearing impaired.
In the present field study, ambient noise levels and the status of group FM-wireless amplification systems were examined in 19 classrooms for the hearing impaired. Classroom noise was judged to be unacceptably high thus justifying the need for group amplification devices. Physical inspection of the group systems revealed defects in approximately one-half of the 28 teacher and 89 student amplification units. The electroacoustic measurements showed wide variability in performance among systems. There also appeared to be no systematic relationship between the degree of hearing loss of the children and the amount of unit gain being employed by each specific amplification system.


Cross-linguistic transfer of phonological skills: a Malaysian perspective.
This study examined the phonological and reading performance in English of Malaysian children whose home language was Bahasa Malaysia (BM). A sample of 69 Malaysian Standard Two pupils (aged 7-8 years) was selected for the study. Since commencing school at the age of 6 years, the children had been learning to read in BM and had subsequently also been learning to read in English for some 12 months. The study was part of a larger scale research programme that fully recognized the limitations of tests that had not been developed and standardized in Malaysia. Nevertheless, as a first step to developing such tests, a comparison with existing norms for the Phonological Assessment Battery (PhAB) and the Wechsler Objective Reading Dimension (WORD) was undertaken in relation to information about the children's L1 and L2 language competencies. Results showed that the children's performance on PhAB was at least comparable to the UK norms while, not surprisingly, they fared less well on WORD. The results are discussed in terms of L1 and L2 transfer, whereby the transparency of written BM and the structured way in which reading is taught in BM facilitates performance on phonological tasks in English. This has implications for identifying children with phonologically based reading difficulties.


Decreased expression of insulin-like growth factor binding protein 6 is associated with gastric adenocarcinoma prognosis.
The present study aimed to investigate the expression and prognostic significance of insulin-like growth factor binding protein 6 (IGFBP-6) in gastric adenocarcinoma. The expression of IGFBP-6 was examined in 263 specimens from gastric adenocarcinoma patients using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemical (IHC) staining. The association between IGFBP-6 expression, clinicopathological factors and clinical outcomes was investigated. Akaike information criterion (AIC) and Harrell's concordance index (c-index) were used to evaluate the accuracy of the predictive prognosis. RT-qPCR and western blotting results showed that IGFBP-6 mRNA expression was lower in the tumors compared with that in adjacent non-tumor tissues. IGFBP-6 showed significantly decreased expression in 170 out of 263 patients based on IHC data and this was associated with a larger tumor size (P<0.001) and poorly-differentiated adenocarcinoma (P=0.001), as well as with palliative gastrectomy (P=0.015). Additionally, decreased expression of IGFBP-6 was associated with stage T3/4a/4b disease and lymph node-positive metastasis (P<0.001). The association between decreased expression and a poor prognosis was revealed by Kaplan-Meier curves. Cox regression model identified IGFBP-6 as an independent prognostic factor. The prognostic value of the model with IGFBP-6 expression (AIC, 924.881; c-index, 0.878) was superior to that without IGFBP-6 expression (AIC, 947.164; c-index, 0.825). In conclusion, IGFBP-6 involves the development and progression of gastric adenocarcinoma, and its decreased expression predicts poor clinical outcomes.


The impact of the COVID-19 pandemic on the mental health of families dealing with attention-deficit hyperactivity disorder.
The COVID-19 pandemic uprooted regular routines forcing many children to learn from home, requiring many adults to work from home, and cutting families off from support outside the home. Public health restrictions associated with the pandemic caused widespread psychological distress including depression and anxiety, increased fear, panic, and stress. These trends are particularly concerning for families raising neuroatypical children such as those with Attention-Deficit Hyperactivity Disorder (ADHD), as these children are already more likely than their typically developing peers to experience comorbid mental health issues, and to experience greater distress when required to stay indoors. Families with children who have ADHD are also at greater risk for experiencing heightened familial stress due to the challenges associated with managing ADHD behavioural symptoms, greater parental discord and divorce, and greater financial difficulties compared to other families. The current study engaged families comprised of at least one child diagnosed with ADHD to elucidate 1) the unique ways that the COVID-19 pandemic affected their mental health and 2) the specific barriers these families faced to maintaining optimal mental wellbeing. A total of 33 participants (15 parent-child dyads) engaged in virtual interviews. Content analysis revealed that the most frequently identified mental health effects for families were increased child anxiety and disconnectedness, as well as deteriorating parental mental health. The most frequently identified barriers to maintaining optimal mental wellbeing were lack of routine, lack of social interaction and social supports, and uncertainty and fear. Findings underscore areas of need during times of large-scale social isolation, specifically for families with children who have ADHD. This work contributes to a growing body of research aimed at creating safeguards to support mental wellbeing for vulnerable families during times of crisis.


Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP Activation and Over-Expression of miR-33.
Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process. An atherosclerosis model was established in apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression. Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder. Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis.


[The use of monoclonal antibodies for the quantitative determination of myoglobin by the solid phase immunoenzyme "sandwich" assay].
A procedure of solid phase single step immunoenzyme assay of the "sandwich" type involving monoclonal antibodies was developed to estimate myoglobin in blood serum of patients, 30 stable hybridomic clones. producing antibodies to not less than six various epitopes of myoglobin, were obtained. Content of myoglobin in blood serum was studied using antibodies of the IgG type to two various epitopes of myoglobin as well as of their conjugates with horseradish peroxidase. The procedure developed enabled to estimate myoglobin in blood serum at concentrations 2-1,600 ng/ml and to analyze 120 preparations within 3 hrs.


[Statistical deviations in high-performance athletes].
Between 1978 and 1984, 1323 high level athletes were tested at the Sports sciences institute of the Swiss federal sports school. During these investigations, several characteristic variations of body statics were measured. Analysis of the pooled data reveal a link of statistical significance between certain sports and several abnormalities of lower limbs static. As it was a retrospective investigation, we cannot be sure of a causal relationship between the reported effects. Our principal aim however was to publish this somewhat extensive set of data, in view of the general dearth of such scientific results. In addition to the type of movement the athletes perform during their sports activity, it is the duration of the exertion which seems to be an important determinant for the presence of an increased number of static abnormalities in certain sports. Endurance running presents an elevated risk of developing both flat foot and splay foot. For football (soccer) and tennis players however, only a subnormal transverse foot arch appears frequently. Alpine skiers on the other hand have an increased risk of longitudinal foot arch insufficiency. The knowledge as to which abnormalities are increasingly present in a given sport is instrumental to enabling an early detection and prophylaxis of these ailments.


Improved Annotations of 23 Differentially Expressed Hypothetical Proteins in Methicillin Resistant S.aureus.
Antibiotic resistant Staphylococcus aureus is a major public health concern effecting millions of people annually. Medical science has documented completely untreatable S. aureus infections. These strains are appearing in the community with increasing frequency. New diagnostic and therapeutic options are needed to combat this deadly infection. Interestingly, around 50% of the proteins in S. aureus are annotated as hypothetical. Methods to select hypothetical proteins related to antibiotic resistance have been inadequate. This study uses differential gene expression to identify hypothetical proteins related to antibiotic resistant phenotype strain variations. We apply computational tools to predict physiochemical properties, cellular location, sequence-based homologs, domains, 3D modeling, active site features, and binding partners. Nine of 23 hypothetical proteins were <100 residues, unlikely to be functional proteins based on size. Of the 14 differentially expressed hypothetical proteins examined, confident predictions on function could not be made. Most identified domains had unknown functions. Six hypothetical protein models had >50% confidence over >20% residues. These findings indicate the method of hypothetical protein identification is sufficient; however, current scientific knowledge is inadequate to properly annotate these proteins. This process should be repeated regularly until entire genomes are clearly and accurately annotated.


Positive stem cell selection--basic science.
Immunologic strategies for removal of malignant cells from autologous marrow grafts by "negative selection" (i.e., "purging") requiring multiple specific monoclonal antibodies for each tumor type. "Positive selection" of marrow stem cells for grafting is a possible alternative strategy, using a monoclonal antibody which selectively recognizes lymphohematopoietic stem cells. The human hematopoietic progenitor cell antigen, CD34, is an integral cell membrane glycoprotein of approximately 115 kD, which has been molecularly cloned and sequenced. Although its function has not been determined, the glycoprotein has been characterized biochemically, including preliminary epitope mapping. Collective results from several laboratories indicate that CD34 monoclonal antibodies (My10, BI-3C5, 12.8, etc.) have the appropriate specificity to warrant testing their utility in positive selection for autologous bone marrow transplantation. First, precursors for all human hematopoietic lineages assayed (including most CFU-GM, BFU-E, CFU-MEG, CFU-EO, CFU-MIX or CFU-GEMM, pre-CFU, CFUBLAST, and terminal transferase+ B [and probably T] lymphoid precursors) are CD34+. Second, only 1.5% (mean) of low density human marrow mononuclear cells express CD34; mature human blood and marrow cells are CD34-. Endothelial cells are the only fixed tissue cells which express CD34. Third, the expression of CD34 in malignancies appears to parallel normal cellular expression: of hematopoietic malignancies, some acute leukemias and chronic myelogenous leukemia blasts are CD34+, but chronic lymphois leukemias, lymphomas, myelomas and non-hematopoietic malignancies are uniformly CD34-. Fourth, it appears feasible to isolate CD34+ cells from clinical marrow harvest samples in large scale, using either columns or immunomagnetic microspheres. Fifth, recent studies in very small numbers of non-human primates and human patients suggest that isolated CD34+ cells include the true hematopoietic stem cell, since transplantation of CD34+ cells, into myeloblated recipients results in at least short-term hematopoietic engraftment. It is anticipated that transplantation of CD34+ marrow cells may have broad applicability in clinical bone marrow transplantation.


Plane wave imaging combined with eigenspace-based minimum variance beamforming using a ring array in ultrasound computed tomography.
Ultrasound computed tomography (USCT) is usually realized with a ring array. It can provide better imaging performance and more tissue information by emitting and receiving the ultrasound signal in different directions simultaneously. However, USCT imaging is usually applied with the synthetic aperture (SA) emission method, which leads to a long scanning time with a large number of elements on the ring array. The echo image can provide the structural information, and has a higher resolution than maps of other parameters in USCT. Hence, we proposed plane wave (PW) imaging for ring array to acquire the echo wave and reduce the scanning time considerably. In this paper, an emitting and receiving process was proposed to realize plane wave imaging with a ring array. With the proposed scanning method, the number of emission events can be reduced greatly. A beamforming method based on the eigenspace-based minimum variance (ESBMV) was also combined with the scanning method. With ESBMV beamformer, the resolution and contrast ratio of reconstruction result can be maintained or even improved under a fewer-emissions condition. We validated the method using both computer simulations with Field II and phantom experiments with a ring array of 512 elements. The Verasonics® system was used to transmit and receive the ultrasound signal in the phantom experiments. According to the results of the experiments, the imaging results will have a better contrast ratio with a higher emitting energy. Additionally, the scanning time with the proposed method can be only one-tenth of that with the SA emission method, while the echo imaging performance still remains at a similar level or even better.


Studies on the regeneration of the skin barrier and the changes in 32P incorporation into the epidermis after stripping.
The epidermis of the rabbit ear was stripped and the effects on percutaneous absorption and 32P incorporation into lipid, TCA-soluble, RNA and DNA fractions in the epidermis was studied for 21 days. Skin penetration by 14C-propylene glycol increased 300-fold immediately after stripping twenty times. Three to five days after stripping, penetration had returned almost to normal levels, but it required several additional days for the barrier function to become normal. The process of regeneration of the skin barrier paralleled the morphological changes in the epidermis but was inconsistent with the biochemical data. A significant increase in 32P incorporation was observed at 10 days, when the hyperplasia had disappeared and percutaneous absorption had returned to normal. The discrepancy between 32P incorporation and morphology or percutaneous absorption after stripping is discussed.